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Cross-presentation enables dendritic cells to present on their MHC class I molecules antigenic peptides derived from exogenous material, through a mechanism that remains partly unclear. It is particularly efficient with long peptides, which are used in cancer vaccines. We studied the mechanism of long-peptide cross-presentation using human dendritic cells and specific CTL clones against melanoma Ags gp100 and Melan-A/MART1. We found that cross-presentation of those long peptides does not depend on the proteasome or the transporter associated with Ag processing, and therefore follows a vacuolar pathway. We also observed that it makes use of newly synthesized MHC class I molecules, through peptide exchange in vesicles distinct from the endoplasmic reticulum and classical secretory pathway, in an SEC22b- and CD74-independent manner. Our results indicate a nonclassical secretion pathway followed by nascent HLA-I molecules that are used for cross-presentation of those long melanoma peptides in the vacuolar pathway. Our results may have implications for the development of vaccines based on long peptides.

Original publication

DOI

10.4049/jimmunol.1501574

Type

Journal article

Journal

J Immunol

Publication Date

15/02/2016

Volume

196

Pages

1711 - 1720

Keywords

Antigen Presentation, Cell Line, Cells, Cultured, Cross-Priming, Dendritic Cells, Histocompatibility Antigens Class I, Humans, Peptides, Proteasome Endopeptidase Complex, T-Lymphocytes, Cytotoxic, Vacuoles, gp100 Melanoma Antigen